Bioequivalence Study Comparing Mucinex Extended-release 600 mg Tablets to Immediate-release Guaifenesin 600 mg in Healthy Volunteers

NCT03644095 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 2009-GGE-02
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Determine bioequivalence, safety and tolerability of guaifenesin extended-release 600 mg (Mucinex® SE) compared to an immediate-release syrup reference product in normal healthy subjects.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (7)

• Maximum Observed Plasma Concentration (Cmax) of Guaifenesin

  Pharmacokinetic Parameter (Cmax) Maximum observed plasma concentration.

  0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2

• Area Under Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUC(0-t)) of Guaifenesin

  Area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration, as calculated by the linear trapezoidal method.

  0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2

• Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUC(0-inf)) of Guaifenesin

  Area under the plasma concentration versus time curve from time 0 to infinity, calculated as AUC 0-t + C last/kel, where C last is the last measurable concentration and kel is the apparent first-order terminal elimination rate constant.

  0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2

• Time to Maximum Observed Concentration (Tmax) of Guaifenesin

  Pharmacokinetic Parameter (Tmax) Time of the maximum observed plasma concentration.

  0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2

• Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin

  Pharmacokinetic Parameter AUCR is the ratio of AUC(0-t) to AUC(0-inf). AUCR = AUC(0-t) / AUC(0-inf)

  0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2

• Apparent Terminal Elimination Rate Constant (Kel) of Guaifenesin

  Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma concentration versus time curve. The parameter was calculated by linear least-squares (LS) regression analysis using the maximum number of points (e.g. 3 or more non-zero plasma concentrations) in the terminal log-linear phase.

  0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2

• Apparent Terminal Elimination Half-life (t1/2) of Guaifenesin

  Apparent first-order terminal elimination half-life, calculated as ln(2)/kel.

  0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2

Secondary Outcomes (1)

• Number of Adverse Events (AE) of Participants

  Upto Day 2

Study Arms (2)

Mucinex® SE 600 mg (extended-release)

EXPERIMENTAL

Single dose of Mucinex® SE extended-release 600 mg bi-layer tablet taken with 240 mL of water after an overnight fast

Drug: Mucinex® SE

Vicks Cough Syrup 200 mg

ACTIVE COMPARATOR

Vicks Cough Syrup for Chesty Coughs 200 mg every 4 hours taken with 240 mL of water after an overnight fast

Drug: Vicks Cough Syrup for Chesty Coughs

Interventions

Mucinex® SE DRUG

Single dose of Mucinex® SE extended-release 600 mg bi-layer tablet

Also known as: guaifenesin bi-layer tablet

Mucinex® SE 600 mg (extended-release)

Vicks Cough Syrup for Chesty Coughs DRUG

Vicks Cough Syrup for Chesty Coughs 15 mL (200 mg guaifenesin q4h) immediate release (IR) syrup

Also known as: guaifenesin

Vicks Cough Syrup 200 mg

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and/or females between the ages of 19 and 55 years, inclusive.
• Females of childbearing potential must be using one of the following acceptable birth control methods:
• Intra-uterine device in place for at least 3 months prior to Day 1 of Period 1 through 30 days beyond study completion;
• Barrier method (condom or diaphragm) with spermicide for at least 7 days prior to screening through 30 days beyond study completion;
• Stable hormonal contraceptive (e.g., oral, depo injection, transdermal patch, or vaginal ring) for at least 3 months prior to Day 1 of Period 1 through 30 days beyond completion of study;
• Abstinence is not an acceptable form of contraception; however, abstinent female subjects may be admitted to the study if they agree, and have signed a statement to the effect, that upon becoming sexually active, will use a condom with spermicide from screening through 30 days beyond completion of the study.
• Females of non-childbearing potential should be surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to study or hysterectomy and/or bilateral oophorectomy at least 3 months prior to Day 1 of Period 1) or postmenopausal \>2 years prior to Day 1 of Period 1. A follicle stimulating hormone (FSH) concentration \>40 miU/mL must be obtained and recorded for any postmenopausal females.
• Good general health as determined by the Principal Investigator's (PI) review of medical history, physical examination, vital sign measurements, electrocardiogram (ECG), and clinical laboratory measures.
• Body weight between 50 - 100 kg and body mass index (BMI) within 18 - 30 kg/m2.
• Non-tobacco users, who have not used nicotine or nicotine-containing products for at least 365 days prior to Day 1 of Period 1.
• Able to read, understand and sign the informed consent after the nature of the study has been explained.
• Negative urine screen for drugs of abuse and alcohol at screening and each check in.
• If female, negative finding on serum pregnancy test at screening and each check-in.
• Non alcohol or drug abuser - non alcohol abuse is defined as history of less than 4 drinks daily. A drink is defined as 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of spirits (i.e., 'hard' liquor such as gin, whiskey, or vodka).

You may not qualify if:

• Clinically significant abnormalities detected by medical history, physical examination, vial sign measurements, ECG, or clinical laboratory findings (as determined by the PI/designee) including a hemoglobin value \<12 gm/dL at screening. If a subject's hemoglobin drops below 11.0 gm/dL during the study, the subject may be dropped from the study at the discretion of the PI.
• Any disease or condition, which could impact absorption, distribution, metabolism, or elimination of the study drugs (as determined by the PI/designee).
• Females who are pregnant or nursing.
• History of sensitivity reaction to guaifenesin.
• Receipt of an investigational drug within 30 days prior to Day 1 of Period 1.
• Abnormal diet (for whatever reason) during the 30 days prior to Day 1 of Period 1.
• Donation of blood or significant loss of blood within 56 days or plasma within 14 days prior to Day 1 of Period 1.
• Known or suspected use of illicit drugs.
• The use of any medication (with the exception of hormonal contraceptives for women of childbearing potential) for 14 days or 5 half-lives of the drug (whichever is longer) prior to Day 1 of Period 1.
• Test positive for Hepatitis B surface antigen, Hepatitis C antibodies, or HIV at Screening.

Sponsors & Collaborators

• Reckitt Benckiser Inc.: lead

MeSH Terms

Interventions

Guaifenesin

Intervention Hierarchy (Ancestors)

Guaiacol; Methyl Ethers; Ethers; Organic Chemicals; Phenyl Ethers; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Clinical Research Director, Clinical Research
• Organization: Reckitt Benckiser Inc.

clinicalrequests@rb.com

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: August 23, 2018
• Study Start: January 16, 2009
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: June 19, 2019
• Results First Posted: June 19, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share